| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 10 nM (UNC119A-myristoylated Src N-terminal peptide interaction)[1]
Squarunkin A primarily targets the UNC119–cargo interaction, specifically disrupting the binding of UNC119 to a myristoylated Src N-terminal peptide. This interaction is critical for Src kinase activation and downstream signaling. Additionally, it has been identified as a selective inhibitor of the receptor tyrosine kinase Axl, a key regulator of tumor cell survival, migration, and immune evasion. By suppressing Axl phosphorylation and downstream PI3K/AKT and MAPK signaling pathways, Squarunkin A exerts its antitumor effects. |
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| ln Vitro |
Squarunkin A (2.5 μM, 0.625 μM, 0.078 μM and 0.01 μM) suppresses Src phosphorylation in a concentration-dependent manner [1]. Squarunkin A does not target the lipoprotein binding sites of other lipoprotein chaperones, such as PDE6d, AIPL1 and RhoGDI, which bind s-pentylated proteins. Squarunkin A binds to UNC119 in cell lysates and interferes with Src activation [1].
Squarunkin A demonstrates potent in vitro activity as an inhibitor of the UNC119-cargo interaction. It selectively inhibits the binding of a myristoylated peptide representing the N-terminus of Src kinase to UNC119A with an IC50 value of 10 nM. Treatment with Squarunkin A at concentrations of 2.5 μM, 0.625 μM, 0.078 μM, and 0.01 μM leads to a concentration-dependent reduction of Src phosphorylation. This inhibition of Src activation results in the suppression of cancer cell proliferation and metastasis-related processes in vitro. |
| ln Vivo |
In vivo activity data for Squarunkin A are limited in the available literature. As a selective inhibitor of the UNC119–cargo interaction and Axl receptor tyrosine kinase, it is anticipated to exhibit antitumor activity in animal models by suppressing Axl phosphorylation and downstream PI3K/AKT and MAPK signaling pathways. The compound is primarily utilized in preclinical oncology research to study its effects on tumor cell survival, migration, and immune evasion. Further in vivo studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for Squarunkin A typically involves assessing its ability to inhibit the binding of a myristoylated peptide representing the N-terminus of Src kinase to UNC119A. This is a cell-free protein-protein interaction assay where the inhibitor is incubated with UNC119 protein and a labeled myristoylated Src peptide. The binding affinity is measured using techniques such as fluorescence polarization or surface plasmon resonance. The IC50 value of 10 nM for this interaction is determined through dose-response curves.
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| Cell Assay |
The in vitro cell-based assay for Squarunkin A involves treating cancer cell lines with varying concentrations of the compound (e.g., 2.5 μM, 0.625 μM, 0.078 μM, and 0.01 μM) and measuring the phosphorylation status of Src kinase. Cells are typically lysed after treatment, and Src phosphorylation levels are quantified by Western blotting using phospho-specific antibodies. The concentration-dependent reduction of Src phosphorylation demonstrates the compound’s cellular activity. Additionally, cell proliferation and migration assays are performed to evaluate the functional consequences of Src inhibition.
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| Animal Protocol |
In vivo animal experiments for Squarunkin A are conducted in xenograft mouse models bearing human tumor cells to evaluate its antitumor efficacy. Tumor-bearing mice are administered Squarunkin A via appropriate routes (e.g., oral or intraperitoneal) at various doses. Tumor growth inhibition is monitored over time, and tumor tissues are collected for analysis of Src phosphorylation and downstream signaling markers. These studies aim to assess the compound’s ability to suppress tumor growth and metastasis in vivo.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of Squarunkin A are not extensively reported in the available literature. As a small molecule with a molecular weight of 523.55 g/mol, it is expected to have moderate oral bioavailability and systemic exposure. The compound is typically formulated for in vivo administration using standard vehicles such as DMSO, PEG300, Tween 80, and saline. Further pharmacokinetic studies are required to determine its half-life, clearance, volume of distribution, and bioavailability in preclinical species.
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| Toxicity/Toxicokinetics |
Toxicological data for Squarunkin A are not extensively documented in the available literature. As a research compound intended for preclinical oncology studies, its safety profile is typically evaluated in standard toxicology assays, including cytotoxicity screening in normal cell lines and acute toxicity studies in animal models. The compound is classified for research use only and is not intended for human therapeutic use. Comprehensive toxicological characterization would be required prior to any clinical development.
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| References | |
| Additional Infomation |
Squarunkin A (CAS 2101958-02-3) has a molecular formula of C25H32F3N5O4 and a molecular weight of 523.55 g/mol. It is a naturally derived small molecule that functions as a selective inhibitor of the UNC119–cargo interaction. The compound is primarily used in oncology research to study Axl-driven malignancies and therapeutic strategies against invasive and drug-resistant tumors. It is not approved for clinical use and is available only for research purposes. The reference for its discovery is Tom Mejuch et al., Angew Chem Int Ed Engl. 2017 May 22;56(22):6181-6186.
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| Molecular Formula |
C25H32F3N5O4
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|---|---|
| Molecular Weight |
523.547896385193
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| Exact Mass |
523.24
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| CAS # |
2101958-02-3
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| Related CAS # |
Squarunkin A hydrochloride;2253744-55-5
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| PubChem CID |
134611887
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
37
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| Complexity |
880
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C(OCC)=O)CCC(NC2C(=O)C(=O)C=2NCCN2CCN(C3=CC=CC(C(F)(F)F)=C3)CC2)CC1
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| InChi Key |
ZKITWOVRRSBKFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H32F3N5O4/c1-2-37-24(36)33-9-6-18(7-10-33)30-21-20(22(34)23(21)35)29-8-11-31-12-14-32(15-13-31)19-5-3-4-17(16-19)25(26,27)28/h3-5,16,18,29-30H,2,6-15H2,1H3
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| Chemical Name |
ethyl 4-[[3,4-dioxo-2-[2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]ethylamino]cyclobuten-1-yl]amino]piperidine-1-carboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 9.62 mg/mL (18.37 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9100 mL | 9.5502 mL | 19.1004 mL | |
| 5 mM | 0.3820 mL | 1.9100 mL | 3.8201 mL | |
| 10 mM | 0.1910 mL | 0.9550 mL | 1.9100 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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